James B. Grogan

Comparison of autogenous vein, dacron and gore—tex in infected wounds

Abstract Autogenous vein, Dacron, and GoreTex were evaluated as arterial replacements in wounds inocumulated with S. aureus. The incidence of wound hemorrhage was similar whether synthetic or autogenous materials were used. Experimentally, this indicates no superiority of prosthetic materials or autogenous substances in infected wounds. Thus, extra-anatomic bypass may have to be considered when vascular replacement is required in infected wounds. If impossible, all must be aware of the posibility of sudden, severe postoperative bleeding.

Stimulating Effect of Fructose 1-6 Diphosphate on the Phagocytic Function of Rat RES and on Human Leukocyte Carbohydrate Metabolism

The phagocytic behavior of the reticuloendothelial system in the rat was assessed by a quantitative technique following fructose-1,6-diphosphate (FDP) administration. In addition, the effect of FDP on the carbohydrate metabolism of human leukocytes was investigated. The rate of colloidal carbon clearance from the blood was increased significantly in the FDP-treated rats as compared to dextrose and saline controls (p <0.001). FDP also attenuated the hepatic decrease of ATP (p <0.005) and creatine phosphate (p <0.005) that has been observed after intravenous administration of colloidal carbon. Carbohydrate metabolism in human leukocytes was enhanced by FDP, with a concomitant increase in ATP content (p <0.001). Experimental evidence suggests that FDP intervenes in the Embden-Meyerhof pathway both as a metabolic regulator and as a high energy substrate. These properties of FDP in stimulating the carbohydrate metabolism have recently been described in man.

Glutaraldehyde-preserved venous valve transplantation in the dog

Transplantation of femoral vein grafts was performed on 33 mongrel dogs to assess graft patency and valvular function after storage in glutaraldehyde. The grafts were removed from the donor, flushed with room temperature heparinized lactated Ringers solution, and then stored in a 0.2% glutaraldehyde solution for 16 hr. At the time of grafting, the veins were again flushed with lactated Ringers and anastomosed orthotopically to the recipient. An arteriovenous fistula was also created. Postoperatively the animals received daily doses of aspirin (2 mg/kg) and dipyridamol (50 mg). The following groups were studied: Group I (n = 10) served as controls and received fresh autografts. Group II (n = 13) received autografts stored for 16 hr in 0.2% glutaraldehyde. Group III (n = 10) received allografts stored similarly in glutaraldehyde for 16 hr. The grafts were monitored for evidence of patency. All grafts were removed for histological evaluation when patency was no longer detected or at the end of 7 weeks. Of the fresh and glutaraldehyde-preserved autografts (Group 1), 100% were patent at 7 weeks, and generally retained valve function. Patency of allografts was only slightly inferior but valve function was disappointingly poor at 7 weeks.

Experimental small bowel transplantation utilizing cyclosporine.

Cyclosporine prolonged the survival of ectopic smallbowel allografts in a canine model. A 9-fold increase inmean survival as compared with controls was obtained. Addition of prednisone to cyclosporine did not result infurther graft prolongation, but improved the gross and histological appearance of the allograft. Monitoring the motility and histology of the allograft appears to beautiful in predicting approaching rejection. Xylose absorption was not helpful in this regard. A new technique for measuring fat absorption in the transplant is described. Following allografting, fat absorption is resumed by 14 days posttransplantation.

Long-term nutritional function of orthotopic small bowel autotransplants

Nutritional function following autografting of the entire small bowel was followed in 11 dogs for 12 months. Although positive nitrogen balance was recovered within a few weeks, the animals did not achieve their preoperative body weight for up to 6 months. Fat and D-xylose absorption remained depressed and never fully recovered. Hematocrit and serum iron did not normalize until the second postoperative month or later. Abnormal serum albumin and albumin/globulin ratio persisted for 12 months. When the mesenteric vein was anastomosed to the vena cava rather than to the portal vein, this group had more severe abnormalities in body weight, hematocrit, total protein, and serum albumin, in addition to a significant rise in liver enzymes. These findings represent a discouraging portent for the functional utility of small bowel transplants.

Allograft implants in the anterior chamber of the eye of the rabbit. Early vascularization and sensitization of the host.

Fifty-eight allografts of skin, 12 of endocrine tissue, and 4 of heterologous tumor became vascularized between 5 and 11 days after implantation in the anterior chamber of rabbit eyes and yet survived for long periods of time. Furthermore, skin allograft implants in the anterior chamber of the eye of the rabbit were capable of specifically immunizing the recipient. Ear skin allografts taken from the donor of the eye implants underwent accelerated rejection in the recipient when grafted as early as 13 days after the eye implantation. A large proportion of these were rejected as white grafts. These findings are inconsistent with presently held views on the immunological mechanisms operative in the anterior chamber of the eye.

TOTAL ORTHOTOPIC SMALL BOWEL TRANSPLANTATION WITH CYCLOSPORINE

The efficacy of immunosuppression including intravenous cyclosporine was assessed in a dog model of total orthotopic small bowel transplantation. Without immunosuppression, allografted animals died before the thirteenth postoperative day. Cyclosporine and prednisone therapy afforded a sixfold increase in survival of allografted animals. Bowel preparation, such as ex-vivo irradiation, treatment of the donor animal with antithymocyte globulin (ATG), or bowel preservation, did not appear to affect survival. However, a preliminary study of combination therapy using azathioprine, ATG, prednisone, and cyclosporine indicated that there were fewer early deaths as compared with other groups. Histologically, allografted bowel showed various degrees of mucosal change to which poorer nutritional aspects were attributed. “Intestinal death” caused by rejection was considered to be the principal cause of death in animals with advanced mucosal changes, in particular those who were long-term survivors. However, other debilitating factors (e.g., superimposed infection, endotoxemia, or possibly graft-versus-host reaction) may be present in nonsurvivors demonstrating fewer pathological changes in the graft.

Viability of stored lungs.

SUMMARY In vitro viability studies (trypan blue) on 21 canine lungs indicated that about 80% of the cells remained viable after 48 hr of storage under hypothermia and hyperbaric oxygen, but that viability had declined sharply by 72 hr. Replantation of the left lung stored by this method was performed in 38 dogs. Ten of 33 animals receiving lungs stored 24 hr were chronic survivors. None of the five dogs receiving lungs stored for a longer interval survived chronically. Seven of the 10 chronic survivors exhibited considerable function of the reimplanted lung as measured by differential bronchospirometry, compliance, and airway resistance tests from 1 to 6 months after reimplantation. The resting cardiac output was not significantly reduced in the chronic survivors studied, but marked pulmonary hypertension developed when the normal right lung was occluded. Contralateral pneumonectomy was performed on six of the chronic survivors. Two lived for 2½ hr and one for 5 hr, all with substantial oxygen uptake by the replanted lung. The major cause of death may have been right heart failure secondary to the pulmonary hypertension which developed.

Twelve-hour and twenty four-hour preservation of small bowel allografts by simple hypothermia. Survival utilizing cyclosporine.

Canine small bowel was harvested and stored by simple hypothermic technique. After 12-and 24-hr storage, respectively, the small bowel graft was allotransplanted into recipients. All animals receiving 12-hr stored grafts (n=9) survived beyond 5 days. In the 24-hr storage group, 67% of the animals (n=9) survived beyond 5 days. Successful storage for such extended periods by simple hypothermia has not been achieved previously. Donor pretreatment with antibiotics as well as extensive intra-luminal irrigation of the harvested small bowel are considered to be important technical features in this successful preservation.

Suppression of graft-versus-host reactions in rats bearing implants in the anterior chamber of the eye.

SUMMARY The graft-versus-host (GVH) response of spleen cells from rats bearing either orthotopic skin grafts or allogeneic implants in the anterior chamber of the eye was evaluated using popliteal lymph node (PLN) assay. When a viable implant remained in the anterior chamber, the spleen cells of these rats produced a popliteal lymph node enlargement in FI hybrids which was approximately 50% of that produced by a similar number of cells from a normal animal. Conversely, the GVH response of spleen cells from orthotopically skin-grafted rats was noted to be significantly increased over the response of spleen cells from normal animals. The decrease in the GVH response of implanted rat spleen cells was a specific reaction and not because of trauma or implantation, since spleen cells from rats bearing syngeneic implants had shown no reduction in their GVH-inducing ability. The PLN weights of rats receiving mixed population of normal and implanted rat spleen cells were always less than the weights observed with an equal number of normal spleen cells. These findings permit the assumption that implant-bearing rats may be lacking or low in cells that induce GVH reactions or that there is a delayed conversion of effector cells after early immune recognition.